RESEARCH ARTICLE A Kinetic Platform to Determine the Fate of Hydrogen Peroxide in Escherichia coli

Hydrogen peroxide (H2O2) is used by phagocytic cells of the innate immune response to kill engulfed bacteria. H2O2 diffuses freely into bacteria, where it can wreak havoc on sensitive biomolecules if it is not rapidly detoxified. Accordingly, bacteria have evolved numerous systems to defend themselves against H2O2, and the importance of these sys-tems to pathogenesis has been substantiated by the many bacteria that require them to establish or sustain infections. The kinetic competition for H2O2 within bacteria is complex, which suggests that quantitative models will improve interpretation and prediction of net-work behavior. To date, such models have been of limited scope, and this inspired us to construct a quantitative, systems-level model of H2O2 detoxification in Escherichia coli that includes detoxification enzymes, H2O2-dependent transcriptional regulation, enzyme deg-radation, the Fenton reaction and damage caused by •OH, oxidation of biomolecules by H2O2, and repair processes. After using an iterative computational and experimental proce-dure to train the model, we leveraged it to predict how H2O2 detoxification would change in response to an environmental perturbation that pathogens encounter within host phago